The nervous system is composed of many neurons connected into complex circuits, largely through carefully choreographed processes of axon guidance. Currently, a major focus is the molecular and cellular mechanisms conveying directionality and specificity in axon pathfinding and target selection.
Axonal connections in the nervous system are highly organized, often patterned along major axes. The nature of anterior-posterior guidance cues has remained elusive until recent years. We found that Wnt family proteins direct a class of ascending sensory axons to project along the spinal cord towards the brain and the descending growth of corticospinal tract axons in the opposite direction. We are examining whether these Wnts are involved in A-P pathfinding of other classes of axons.
One common type of connection is topographic mapping, whereby positional orders of neurons are smoothly and continuously mapped to their targets. Classical studies and computational modeling predicted at least two counterbalancing forces are required to make a map. We found that Wnt3 is a force that guides retinal ganglion cell axons to terminate laterally to counterbalance the medially directing force, ephrinB1. We are testing the role of Wnts in topographic connections in different brain areas and whether the model of two-molecular-gradient model holds true in other map formation.
How intracellular signaling pathways lead to turning of growth cones in response to concentration gradients of guidance cues remains largely unknown. Even less clear is how growth cones change responsiveness at intermediate targets. We are using Wnt signaling as a tool to understand how intracellular pathways are activated and how they work together to orchestrate coordinated changes within a cell.
Neuronal positioning is an important step in neural circuit development. We are studying neuronal migration during cortical lamination. |
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Zou Y. (2009). Axons find their way in the snow. Development 2009 136:2135-2139.
Stoeckli E, Zou Y. (2009). How are neurons wired to form functional and plastic circuits? Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity. EMBO Rep. 2009 Apr;10(4):326-30. Epub 2009 Mar 20.
Salinas PC, Zou Y. (2008). Wnt signaling in neural circuit assembly. Annual Review of Neuroscience. 31:339-58.
Yaobo Liu, Xiaofei Wang, Chin-Chun Lu, Rachel Kerman, Oswald Steward, Xiao-Ming Xu, and Yimin Zou. (2008). Repulsive Wnt Signaling Inhibits Axon Regeneration after CNS Injury. Journal of Neuroscience. 28: 8376-8382.
Alex M. Wolf, Anna I. Lyuksyutova, Ali G. Fenstermaker, Beth Shafer, Charles G. Lo, and Yimin Zou. (2008). Phosphatidylinositol-3-Kinase-Atypical Protein Kinase C Signaling Is Required for Wnt Attraction and Anterior-Posterior Axon Guidance. Journal of Neuroscience. 28: 3456-3467.
Zou Y., Lyuksyutova AI. (2007) Morphogens as conserved axon guidance cues. Curr Opin Neurobiol. Feb;17(1):22-8.
Yimin Zou. (2006). Navigating the anterior-posterior axis with Wnts. Neuron. 49(6):787-9.
Adam Schmitt, Jun Shi, Alex Wolf, Chin-Chun Lu, Leslie A. King and Yimin Zou. (2006). Wnt-Ryk signaling mediates medial-lateral retinotectal topographic mapping. Nature 439(7072);31-7.
Lee Fradkin, Gian Garriga , Patricia C. Salinas, John Thomas, Xiang Yu and Yimin Zou. (2005) Wnt signaling in neural circuit development (minireview). Journal of Neuroscience. 25(45):10376-10378.
Yaobo Liu, Jun Shi, Chin-Chun Lu, Zheng Bei Wang, Anna I. Lyuksyutova, Xuejun Song and Yimin Zou. (2005) Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract. Nature Neuroscience. 8(9):1151-9.
Yimin Zou (2004). Wnt signaling in axon guidance (review). Trends in Neuroscience; 27(9): 528-532.
Yimin Zou, Florian Engert and Huizhong W. Tao. (2004). The Assembly of Neural Circuits (Meeting Report). Neuron, 43(2):159-163.
Anna I. Lyuksyutova, Chin-Chun Lu, Nancy Milanesio, Leslie A. King, Nini Guo, Yanshu Wang, Jeremy Nathans, Marc Tessier-Lavigne and Yimin Zou. (2003) Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science, 302:1984-1988.
Elke Stein, Yimin Zou, Mu-ming Poo, and Marc Tessier-Lavigne. (2001). Netrin-1 binds DCC to stimulate axon outgrowth and turning independent of adenosine A2B receptor activation. Science, 291 (5510):1976-82.
Yimin Zou, Esther Stoeckli, Hang Chen, and Marc Tessier-Lavigne. (2000). Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord Cell, 102:363-375.
Hang Chen, Anil Bagri, Joel A. Zupicich, Yimin Zou, Esther Stoeckli, Samuel J. Pleasure, Daniel H. Lowenstein, William C. Skarnes, Alain Chedotal, and Marc Tessier-Lavigne. (2000). Neuropilin-2 regulates the development of select cranial and sensory nerves and hippocampal mossy fiber projections. Neuron, 25(1): 43-56.
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